Cerium(3+) acetate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 January 2017 to 01 February 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2017

Report date:

2017

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Cerium(3+) acetate

EC Number:

208-654-0

EC Name:

Cerium(3+) acetate

Cas Number:

537-00-8

Molecular formula:

C2H4O2.1/3Ce

IUPAC Name:

cerium(3+) triacetate

Test material form:

solid: granular

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Batch No.of test material: CEACK1/16
- Expiration date of the lot/batch: 17 October 2018:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: room temperature in the dark over silica gel

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: For the purpose of the study the test material was freshly prepared, as required, as a suspension in arachis oil BP. The test material was formulated within 2 hours of being applied to the test system.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8 to 12 weeks
- Weight at study initiation: 165 to 187 g
- Fasting period before study: Animals had an overnight fast immediately before dosing and for approximately 3 to 4 hours after dosing.
- Housing: In groups of up to 4 in suspended solid-floor polypropylene cages furnished with woodflakes.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 19 to 25 °C
- Humidity: 30 to 70 %
- Air changes: At least 15 changes per hour
- Photoperiod: 12 hours continuous light and 12 hours continuous dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Remarks:

(BP)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 300 and 2000 mg/kg bw
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: Arachis oil BP was used because the test material did not dissolve/suspend in distilled water.

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

A single animal was treated at 300 mg/kg bw.
Five animals were treated at 2000 mg/kg bw.

Control animals:

no

Details on study design:

OBSERVATIONS
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for 14 days. Morbidity and mortality checks were made twice daily, early and late during normal working days, and once daily at weekends and public holidays. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14.
- Necropsy of survivors performed: At the end of the observation period the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

DATA EVALUATION
- Evaluation of data included identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of evident toxicity were described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were also identified.
- Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test material was made.

Statistics:

No statistical analysis was done in conjunction with this study.

Results and discussion

Preliminary study:

DOSE LEVEL 300 MG/KG BW
- There was no mortality.
- No signs of systemic toxicity were noted during the observation period.
- The animal showed expected gains in body weight over the observation period.
- No abnormalities were noted at necropsy.

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: 2000 mg/kg bw was the highest dose tested

Mortality:

There were no deaths.

Clinical signs:

other: Noisy respiration was noted in two animals during the day of dosing and persisted in one animal 1 day after dosing. No signs of systemic toxicity were noted in three animals during the observation period. Individual clinical observations can be seen in Ta

Gross pathology:

No abnormalities were noted at necropsy.

Any other information on results incl. tables

Table 1: Individual Clinical Observations and Mortality Data - 2000mg/kg

Dose Level mg/kg	Animal Number and Sex	Effects Noted After Dosing (Hours)				Effects Noted During Period After Dosing (Days)
		½	1	2	4	1	2	3	4	5	6	7	8	9	10	11	12	13	14
2000	2-0 Female	0	0	Rn	Rn	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-0 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-1 Female	0	Rn	Rn	Rn	Rn	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-2 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0
	3-3 Female	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0	0

0=  No signs of systemic toxicity

Rn =Noisy respiration

Applicant's summary and conclusion

Interpretation of results:

other: Not classified in accordance with EU criteria

Conclusions:

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.

Executive summary:

The acute oral toxicity of the test material was determined in accordance with the standardised guidelines OECD 420 and EU Method B1 bis, under GLP conditions using female Wistar rats.

The test material was formulated in Arachis oil BP, this vehicle was used because the test material did not dissolve/suspend in distilled water.

Following a sighting test at dose levels of 300 mg/kg and 2000 mg/kg, a further group of four fasted females was given a single oral dose of test material, as a suspension in arachis oil BP, at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

During the observation period there were no deaths. Noisy respiration was noted in two animals treated at a dose level of 2000 mg/kg. No other signs of systemic toxicity were noted. All animals showed expected gains in body weight and no abnormalities were noted at necropsy.

Under the conditions of the study, the acute oral median lethal dose (LD50) of the test material in the female Wistar strain rat was estimated to be greater than 2000 mg/kg body weight.